In silico preclinical trials: methodology and engineering guide to closed-loop control in type 1 diabetes mellitus

J Diabetes Sci Technol. 2009 Mar 1;3(2):269-82. doi: 10.1177/193229680900300207.


This article sets forth guidelines for in silico (simulation-based) proof-of-concept testing of artificial pancreas control algorithms. The goal was to design a test procedure that can facilitate regulatory approval [e.g., Food and Drug Administration Investigational Device Exemption] for General Clinical Research Center experiments without preliminary testing on animals. The methodology is designed around a software package, based on a recent meal simulation model of the glucose-insulin system. Putting a premium on generality, this document starts by specifying a generic, rather abstract, meta-algorithm for control. The meta-algorithm has two main components: (1) patient assessment and tuning of control parameters, i.e., algorithmic processes for collection and processing patient data prior to closed-loop operation, and (2) controller warm-up and run-time operation, i.e., algorithmic processes for initializing controller states and managing blood glucose. The simulation-based testing methodology is designed to reveal the conceptual/mathematical operation of both main components, as applied to a large population of in silico patients with type 1 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Blood Glucose / physiology*
  • Computer Simulation*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / therapy*
  • Food
  • Humans
  • Insulin / physiology
  • Insulin Infusion Systems
  • Pancreas, Artificial*


  • Blood Glucose
  • Insulin